Humanized bispecific antibody (mPEG x HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer

Yi-An Cheng, Tung-Ho Wu, Yun-Ming Wang, Tian-Lu Cheng, I-Ju Chen, Yun-Chi Lu, Kuo-Hsiang Chuang, Chih-Kuang Wang, Chiao-Yun Chen, Rui-An Lin, Huei-Jen Chen, Tzu-Yi Liao, En-Shuo Liu, Fang-Ming Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG x HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity.

Result: We used a one-step formulation to rapidly modify the nanoprobes with mPEG x HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The alpha HER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2(++)) but not MCF7/neo1 cells (HER2(+/-)). The alpha HER2/Lipo-DiR and alpha HER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2(++)). In in vivo imaging, alpha HER2/Lipo-DiR and alpha HER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors.

Conclusion: mPEG x HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

Original languageEnglish
Article number118
Number of pages12
JournalJournal of Nanobiotechnology
Volume18
Issue number1
DOIs
StatePublished - 27 Aug 2020

Keywords

  • Bispecific antibody
  • PEGylated nanoparticle
  • Contrast agent
  • Multimodality image
  • Polyethylene glycol
  • Anti-PEG antibody
  • One-step formulation
  • Tumor specificity
  • Cancer image
  • THERAPEUTIC-EFFICACY
  • IMMUNOGENICITY
  • DOXORUBICIN
  • CELLS

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